U.S. patent application number 15/125079 was filed with the patent office on 2017-01-19 for system with an electromagentic field generator with coils for treating tumors and a method for treating tissue.
This patent application is currently assigned to The United States of America, as represented by the Secretary, Department of Health and Human Serv. The applicant listed for this patent is The United States of America, as represented by the Secretary, Department of Health and Human Serv, The United States of America, as represented by the Secretary, Department of Health and Human Serv. Invention is credited to Peter J. Basser.
Application Number | 20170014637 15/125079 |
Document ID | / |
Family ID | 52875253 |
Filed Date | 2017-01-19 |
United States Patent
Application |
20170014637 |
Kind Code |
A1 |
Basser; Peter J. |
January 19, 2017 |
SYSTEM WITH AN ELECTROMAGENTIC FIELD GENERATOR WITH COILS FOR
TREATING TUMORS AND A METHOD FOR TREATING TISSUE
Abstract
Treatment apparatus includes a plurality of coils configured to
generate time-varying magnetic fields that induce electric fields
within a subject. In one example, electric field strengths of at
least 1 V/cm are produced in brain tissues exhibiting Glioblastoma
Multiforme (GBM). Fields are applied based on computer-assisted
modeling using electromagnetic characteristics of the brain, and
tissue locations identified as exhibiting disease using imaging
data. A head mounted assembly of coils can be used for convenient,
portable treatment.
Inventors: |
Basser; Peter J.;
(Washington, DC) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
The United States of America, as represented by the Secretary,
Department of Health and Human Serv |
Bethesda |
MD |
US |
|
|
Assignee: |
The United States of America, as
represented by the Secretary, Department of Health and Human
Serv
Bethesda
MD
|
Family ID: |
52875253 |
Appl. No.: |
15/125079 |
Filed: |
March 17, 2015 |
PCT Filed: |
March 17, 2015 |
PCT NO: |
PCT/US2015/021066 |
371 Date: |
September 9, 2016 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
61954494 |
Mar 17, 2014 |
|
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A61N 2/02 20130101; A61N
1/40 20130101; A61N 2/006 20130101 |
International
Class: |
A61N 2/02 20060101
A61N002/02; A61N 1/40 20060101 A61N001/40; A61N 2/00 20060101
A61N002/00 |
Claims
1. A system, comprising: a plurality of coils; and an
electromagnetic field generator that energizes the plurality of
coils so as to apply a tumor treating field (TTF) to a specimen
region, wherein the TTF has a time varying magnetic field component
that induces an electric field of magnitude of at least 0.1 V/cm at
a frequency of between 50 kHz and 500 kHz.
2. The system of claim 1, wherein the specimen region is associated
with a tumor.
3. The system of claim 2, wherein the tissue region is associated
with a brain tumor.
4. The system of claim 1, wherein the electromagnetic field
generator energizes the plurality of coils so as to apply the TTF
to the specimen region along a plurality of axes.
5. The system of claim 1, wherein the electromagnetic field
generator sequentially energizes the plurality of coils so as to
sequentially apply the TTF to the specimen region along at least
two axes.
6. The system of claim 5, wherein the electromagnetic field
generator energizes the plurality of coils so that the TTF is
applied at a plurality of frequencies between 50 kHz and 500
kHz.
7. The system of claim 1, further comprising a rigid shell that is
shaped to at least partially enclose the specimen region, wherein
the plurality of coils is secured to the rigid shell.
8. The system of claim 1, wherein the rigid shell is a portion of a
helmet.
9. The system of claim 1, wherein the coils of the plurality of
coils are flexibly interconnected so as to be wrappable about the
specimen region.
10. The system of claim 9, wherein coils are energized by the
electromagnetic field generator so as to produce a time-varying
magnetic field that produces an induced electric field magnitude of
at least 0.5, 1.0, 2, 5, 10, or 100 V/cm.
11. A method, comprising: identifying a tissue to be exposed to a
treatment electromagnetic field; and applying the treatment
electromagnetic field to a portion of the tissue, the treatment
electromagnetic field having a time-varying magnetic field
component that produces an induced electric field having an
effective magnitude of at least 0.5 V/cm at a frequency of between
about 50 kHz and 500 Hz in the region to be exposed.
12. The method of claim 11, further comprising determining the
applied treatment electromagnetic field based on electrical
characteristics of the tissue determined from an image of the
tissue.
13. The method of claim 11, wherein the treatment electromagnetic
field is applied along at least two axes.
14. The method of claim 13, wherein the tissue is a portion of a
patient brain.
15. The method of claim 14, further comprising applying the
treatment electromagnetic field along a plurality of axes.
16. The method of claim 15 further comprising applying the
treatment electromagnetic field at a plurality of frequencies in
the range of 50 kHz to 500 kHz.
17. The method of claim 14, wherein the treatment electromagnetic
field is applied so as to have an effective duration of at least 10
ms, 100 ms, 1 s, 10 s, 100 s , or 1000 s.
18. The method of claim 11, wherein the treatment electromagnetic
field is applied with coils that are fixed with respect to the
tissue.
19. The method of claim 11, further comprising applying the
treatment electromagnetic field along different axes by selectively
energizing corresponding coils.
20. The method of claim 11, further comprising determining the
treatment electromagnetic field based on an electrical model of the
tissue that includes at least one tissue permittivity and at least
one tissue conductivity.
21. At least one non-transitory computer readable medium comprising
computer-executable instructions for a method of applying treatment
electromagnetic fields to a tissue, the method comprising:
selecting a portion of the tissue exhibiting cancer; generating a
sequence of electrical currents and coupling the sequence of
electrical currents to at least one coil so as to produce the
treatment electromagnetic fields in the selected portion of the
tissue, wherein the treatment electromagnetic field includes a
time-varying magnetic field that produces an electric field having
a magnitude of at least 0.1 V/cm.
22. The at least one computer readable medium of claim 21, wherein
the electrical currents have magnitudes such that the treatment
electromagnetic fields have time varying magnetic field components
that produce an induced electric field magnitude of at least 0.5,
1.0, 2, 5, 10, or 100 V/cm.
23. The at least one computer readable medium of claim 21, wherein
the treatment electromagnetic fields are applied along a least two
axes.
24. The at least one computer readable medium of claim 21, wherein
the electrical currents are selected based on a sequence of
electrical currents includes electrical currents at least two
frequencies between 50 kHz and 1 MHz.
25. The at least one computer readable medium of claim 23, wherein
the selected portion of the brain is identified as exhibiting
GBM.
26. The at least one computer-readable medium of claim 21, wherein
the method further comprises estimating an electromagnetic field
distribution in the tissue based on a tissue image and at least one
tissue permittivity and at least one tissue conductivity, wherein
the sequence of electrical currents is based on the estimated
electromagnetic field distribution.
27. The at least one computer-readable medium of claim 26, wherein
the tissue image is an MR image.
28. The method of claim 11, wherein the tissue comprises a
Glioblastoma Multiforme brain tumor.
Description
FIELD
[0001] The disclosure pertains to treatment of Glioblastoma
Multiforme or other cancers using induced electromagnetic
fields.
BACKGROUND
[0002] Treatment of cancer in the brain presents significant
challenges. It can be difficult to administer medications in an
effective manner that permits therapeutic amounts to reach brain
areas requiring treatment. In other cases, surgical or other
mechanical interventions may be precluded due to the location of
the diseased area. For example, access to the diseased area may be
possible only by unacceptable injury to other brain areas.
Conventional treatments based on surgery and chemotherapy are not
effective in achieving long-term patient survival.
[0003] Treatment of Glioblastoma Multiforma (GBM), the most common
and lethal primary brain cancer, has been previously proposed based
on electric fields applied with an array of capacitively coupled
electrodes placed on a patient's scalp. Oscillating electric fields
at frequencies of 100-300 kHz and magnitudes of 1-3 V/cm have been
demonstrated to disrupt mitotic division in GBM cells in culture.
Such tumor treating fields (TTFs) have shown promise in the
treatment of GBM. One significant problem with this approach is the
difficulty in accurately targeting the necessary electric fields to
diseased tissues. Both the electrodes and currents needed for
treatment may impact patient comfort. Currently, the patient's hair
must be shaven and electrodes must be affixed to the skin. The high
currents required to penetrate the scalp and skull into the brain
parenchyma often result in skin rashes. In some cases, currents
intended for treatment may be shunted away from the diseased
tissues. Thus, despite significant advances in chemotherapy,
surgical procedures, and TTF-based treatments, alternative
approaches are still needed.
SUMMARY
[0004] According to some examples, systems comprise a plurality of
coils and an electromagnetic field generator that energizes the
plurality of coils so as to apply a tumor treating field (TTF) to a
specimen region. The TTF has a time-varying magnetic field
component that induces an electric field of magnitude of at least
0.1 V/cm at a frequency of between 50 kHz and 500 kHz. In some
embodiments, the specimen region is associated with a tumor, and in
particular examples, at least one brain tumor. In some
alternatives, the electromagnetic field generator energizes the
plurality of coils so as to apply the TTF to the specimen region
along a plurality of axes. In other examples, the electromagnetic
field generator sequentially energizes the plurality of coils so as
to sequentially apply the TTF to the specimen region along at least
two axes. According to other embodiments, the electromagnetic field
generator energizes the plurality of coils so that the TTF is
applied at a plurality of frequencies between 50 kHz and 500 kHz.
In one example, a rigid shell is shaped to at least partially
enclose the specimen region, wherein the plurality of coils is
secured to the rigid shell. In still other examples, the coils of
the plurality of coils are flexibly interconnected so as to be
wrappable about the specimen region. In yet other alternatives, the
coils are energized by the electromagnetic field generator so as to
produce a time-varying magnetic field that produces an induced
electric field magnitude of at least 0.5, 1.0, 2, 5, 10, or 100
V/cm.
[0005] Methods comprise identifying a tissue to be exposed to a
treatment electromagnetic field. The treatment electromagnetic
field is applied to at least a portion of the tissue, the treatment
electromagnetic field having a time-varying magnetic field
component that produces an induced electric field having an
effective magnitude of at least 0.5 V/cm at a frequency of between
about 50 kHz and 500 Hz in the region to be exposed. In some cases,
the applied treatment electromagnetic field is based on electrical
characteristics of the tissue determined from an image of the
tissue. In other examples, the treatment electromagnetic field is
applied along at least two axes. In one example, tissue is at least
a portion of a patient brain. In still other alternatives, the
treatment electromagnetic field is applied along a plurality of
axes and at a plurality of frequencies in the range of 50 kHz to
500 kHz. In some embodiments, the treatment electromagnetic field
is applied so as to have an effective duration of at least 10 ms,
100 ms, 1 s, 10 s, 100 s, or 1000 s. In some cases, the treatment
electromagnetic fields are applied sequentially or simultaneously
at a plurality of frequencies, and differing coils or sets of coils
can be switched so as to apply the treatment electromagnetic
fields. In some examples, a swept frequency electromagnetic field
is applied using one, two or more coils or coils sets that are
sequentially or simultaneously energized. In particular examples,
the treatment electromagnetic field is applied with coils that are
fixed with respect to the tissue and the treatment electromagnetic
field is applied along different axes by selectively energizing
corresponding coils. In still other embodiments, the treatment
electromagnetic field is determined based on an electrical model of
the tissue that includes at least one tissue permittivity and at
least one tissue conductivity.
[0006] At least one non-transitory computer readable medium
comprises computer-executable instructions for a method of applying
treatment electromagnetic fields to a tissue. The method comprises
selecting a portion of the tissue exhibiting cancer and generating
a sequence of electrical currents and coupling the sequence of
electrical currents to at least one coil so as to produce the
treatment electromagnetic fields in the selected portion of the
tissue. Typically, the treatment electromagnetic field includes a
time-varying magnetic field that induces a time-varying electric
field having a magnitude of at least 0.1 V/cm. In other examples,
the electrical currents have magnitudes such that the treatment
electromagnetic fields have time varying magnetic field components
that produce an induced electric field magnitude of at least 0.5,
1.0, 2, 5, 10, or 100 V/cm. In some examples, the treatment
electromagnetic fields are applied along a least two axes and the
electrical currents are selected based on a sequence of electrical
currents that includes electrical currents at at least two
frequencies between 50 kHz and 1 MHz. In still further examples,
the tissue is a portion of the brain is identified as exhibiting
GBM. In other alternatives, methods further comprise estimating an
electromagnetic field distribution in the tissue based on a tissue
image and at least one tissue permittivity and at least one tissue
conductivity, wherein the sequence of electrical currents is based
on the estimated electromagnetic field distribution. In some
embodiments, the tissue image is an MR image.
[0007] The foregoing and other features and advantages of the
disclosed technology will become more apparent from the following
detailed description, which proceeds with reference to the
accompanying figures.
BRIEF DESCRIPTION OF THE DRAWINGS
[0008] FIG. 1 is a block diagram of a representative system for
applying transcranial electromagnetic fields.
[0009] FIG. 2 illustrates a representative method of applying
transcranial electromagnetic fields.
[0010] FIGS. 3A-3B illustrate a representative apparatus arranged
to apply magnetic fields to selected regions of interest with a
plurality of coils.
[0011] FIG. 4 illustrates a representative apparatus arranged to
secure a plurality of transcranial electromagnetic field generators
to a helmet.
[0012] FIG. 5 illustrates a representative treatment apparatus that
includes a transceiver configured to communicate with a mobile
computing device.
[0013] FIG. 6 illustrates an alternative head-mounted treatment
apparatus.
[0014] FIG. 7 illustrates a user interface for providing treatment
data for determination of drive signals for producing treatment
fields.
[0015] FIG. 8 illustrates a representative computing environment
for implementation of the disclosed methods and apparatus.
[0016] FIG. 9 illustrates a representative mobile computing device
configured for use in conjunction with determination and
application of treatment fields.
[0017] FIG. 10 illustrates cloud-based provisioning of treatment
fields.
[0018] FIG. 11 illustrates a representative coil assembly.
[0019] FIG. 12 illustrates exposure of a specimen region along
multiple axes using associated coils.
[0020] FIG. 13 illustrates a planned exposure method.
DETAILED DESCRIPTION
[0021] As used in this application and in the claims, the singular
forms "a," "an," and "the" include the plural forms unless the
context clearly dictates otherwise. Additionally, the term
"includes" means "comprises." Further, the term "coupled" does not
exclude the presence of intermediate elements between the coupled
items.
[0022] The systems, apparatus, and methods described herein should
not be construed as limiting in any way. Instead, the present
disclosure is directed toward all novel and non-obvious features
and aspects of the various disclosed embodiments, alone and in
various combinations and sub-combinations with one another. The
disclosed systems, methods, and apparatus are not limited to any
specific aspect or feature or combinations thereof, nor do the
disclosed systems, methods, and apparatus require that any one or
more specific advantages be present or problems be solved. Any
theories of operation are to facilitate explanation, but the
disclosed systems, methods, and apparatus are not limited to such
theories of operation.
[0023] Although the operations of some of the disclosed methods are
described in a particular, sequential order for convenient
presentation, it should be understood that this manner of
description encompasses rearrangement, unless a particular ordering
is required by specific language set forth below. For example,
operations described sequentially may in some cases be rearranged
or performed concurrently. Moreover, for the sake of simplicity,
the attached figures may not show the various ways in which the
disclosed systems, methods, and apparatus can be used in
conjunction with other systems, methods, and apparatus.
Additionally, the description sometimes uses terms like "produce"
and "provide" to describe the disclosed methods. These terms are
high-level abstractions of the actual operations that are
performed. The actual operations that correspond to these terms
will vary depending on the particular implementation and are
readily discernible by one of ordinary skill in the art.
[0024] In some examples, values, procedures, or apparatus' are
referred to as "lowest", "best", "minimum," or the like. It will be
appreciated that such descriptions are intended to indicate that a
selection among many used functional alternatives can be made, and
such selections need not be better, smaller, or otherwise
preferable to other selections.
[0025] Some examples below are described with reference to
Glioblastoma Multiforme (GBM), a form of brain cancer. However, the
disclosed methods and apparatus can be configured for use in other
applications as well.
[0026] The disclosed methods and apparatus generally provide
moderate frequency electric fields or tumor treating fields (TTFs)
sufficient to interfere with mitosis or possibly other cellular and
extracellular processes that allow cancer cells to divide and grow.
The disclosed methods and apparatus generally target rapidly
dividing cells. TTFs are generally applied at frequencies of a few
kHz and typically do not produce neural stimulation as a neural
stimulation threshold rises dramatically with frequency, so that at
TTF (kHz) frequencies, neurons tend not to fire. As used herein,
TTF refers to an electric and/or magnetic field at frequencies
between 1 kHz and 1 MHz, 2 kHZ and 1 MHz, 50 kHz and 1 MHz, 100 kHz
and 1 MHz, 10 kHz and 1 MHz, 20 kHZ and 1 MHz, 50 kHz and 750 kHz,
and 50 kHz and 500 MHz. Higher frequency fields are generally less
useful due to, in some cases, lesser penetration into tissues,
tissue heating, or tissue ablation. Lower frequency fields tend to
produce neural and muscular stimulation. However, in some
applications, such lower or higher frequency fields can be used. In
addition, TTFs are generally associated with electric field
strengths of between about 1-3 V/cm, but lesser or greater field
strengths can be used, typically at least about 0.01 V/cm, 0.1
V/cm, 0.2 V/cm, or 0.5 V/cm. In some cases, portable or wearable
apparatus that produce TTFs permit convenient, long-term exposure
to TTFs so that high field strengths are not necessary for
effective treatment. Induced AC fields in the kHz range can be
produced with current-carrying coils placed over the scalp--outside
the brain--to generate TTFs. In general, current-carrying coils can
be placed outside of the body to induce electric fields in a
selected region of the body. While not required, in some examples,
specialized circuits can be used for energy storage are used, to
reduce weight and size of treatment devices, improving portability
and ease of use, and in some cases, making treatment apparatus
wearable.
[0027] In an alternating electric field, charges and polar
molecules are subjected to forces of alternating direction so that
ionic flows and dipole rotate. These oscillations may hamper
mitosis by interfering with formation of a normal functioning
mitotic spindle as tubulin units may align with an applied electric
field rather than the filament axis. Polymerization of tubulin
subunits is necessary for the formation of functional mitotic
spindles (microtubules) that are essential for the successful
completion of mitosis. This could also explain the mitotic arrest
of TTF-treated cells.
[0028] Cellular morphology during cytokinesis resembles an
hourglass shape as the two daughter cells are forming. In the
presence of TTFs, a non-uniform intracellular electric field is
created which is characterized by a higher field intensity at the
furrow between the dividing cells. This non-uniform field exerts
unidirectional forces on polarizable charged macromolecules and
organelles, a process termed dielectrophoresis. Those forces could
interfere with spindle tubulin orientation and the
dielectrophoretic (DEP) force could induce particles toward or away
from the furrow. Cytoplasmatic components and organelles may pile
up at the furrow within a few minutes, interfering with cytokinesis
and possibly leading to incomplete cell division and eventual cell
destruction. These proposed physical mechanisms are likely
mechanisms for producing an anti-mitotic effect but other
mechanisms electric-field mediated mechanisms may also cause this
anti-mitotic effect. However, the disclosed methods and apparatus
do not require such physical mechanisms, and these proposed
mechanisms are provided only to illustrate some possibilities. The
claimed methods and apparatus are not to be limited by any such
physical mechanisms.
[0029] While the disclosed examples are generally described with
reference to treatment of brain cancer, such induced TTFs can be
used to treat other cancers in the body, such as in the torso
(lungs) and even in deep tissue. For example, similar methods and
apparatus can use specialized coils intended for different body
areas, such as the neck, torso or limbs. In some cases, coils for
different areas are substantially the same, but multiple coils are
provided in different arrangements and are secured so as to be
suited for placement at a selected body location. Some applications
include treatment of human melanoma, glioma, cancers of the lung,
prostate, kidney, pancreas, and breast, mouse adenocarcinoma and
melanoma, and rat glioma, and treatment of similar diseases in
humans or in veterinary applications. In addition, the disclosed
methods and apparatus can be used in other applications in which
cell division, cell proliferation, tumor growth, and/or
angiogenesis is to be inhibited or disrupted. Disruption of
angiogenesis could be useful in controlling or treating so-called
wet macular degeneration. Rapid growth of neurons in the brain may
be related to autism, and disruption or hindering of cell division
may be applicable during development as a means to reduce local
cell proliferation. Application of TTFs is associated with
prolonged and abnormal mitosis in vitro, and cell death subsequent
to cytokinesis.
[0030] In general, induced TTFs permit exposure and/or treatment of
selected specimen regions so as to interfere with cell division.
TTF exposures can be advantageous in that longer duration, higher
field exposures can be obtained by limiting exposure to a selected
region. In addition, targeting exposures to a specific region tends
to reduce any unwanted effects associated with exposure.
[0031] Several mechanisms may be responsible for the anti-mitotic
effect produced by exposure to TTFs. TTFs are associated with
bidirectional ion flows and oscillations of dipoles. TTFs can
interfere with formation of a normal functioning mitotic spindle as
tubulin subunits are forced to align with an applied field rather
than with a filament axis. Thus, their main function during
mitosis, which is to generate the spatially organized microtubule
spindle by precise choreographed alignment, is interrupted by
external electric fields, since the tubulin subunits are forced to
align with the impressed electric field rather than with the
filament axis. Polymerization of tubulin subunits is necessary for
formation of functional mitotic spindles (microtubules) that are
essential for the successful completion of mitosis. This effect
could also explain the mitotic arrest of TTF-treated cells.
[0032] Alternatively, TTFs may be associated with a
dielectrophoretic effect. Cellular morphology during cytokinesis
resembles an hourglass shape as the two daughter cells are forming.
In the presence of TTFs, a non-uniform intracellular electric field
is created which is characterized by a higher field intensity at a
furrow between the dividing cells. It is believed that this
non-uniform field exerts unidirectional forces on polarizable
macromolecules and organelles, a process termed dielectrophoresis.
Those forces interfere with spindle tubulin orientation and it was
speculated that the DEP force moves particles toward the furrow.
Cytoplasmatic organelles would accumulate at the cleavage furrow
within a few minutes, interfering with cytokinesis and possibly
leading to cell destruction.
[0033] The above-noted and other responses of cells to induced
electric fields depend on tissue and cell structures, including
orientation, dielectric constants, and conductivities. For example,
permittivity and conductivity of tumor cells tend to be higher than
surrounding tissues due to their higher water content. Glial cells
can have very different dielectric properties, and induced field
strength and frequency can be selected based on such specimen
characteristics.
[0034] As disclosed herein, various types of imaging apparatus can
be configured to produce specimen images based on specimen
interrogation with acoustic waves, photons, electromagnetic
radiation, or application of electric and/or magnetic fields. As
used herein, an image refers to a viewable image of a specimen or a
portion thereof as well as a stored representation of an image.
Stored images can be in one or more computer-readable media as an
image file in a JPEG or other format. Images can be stored locally
(i.e., at a location near the specimen) or stored for retrieval via
a local area network or a wide area network such as the internet.
For convenience, examples based on two dimensional images are
described, but in other examples, one dimensional (line) images,
single point images, or three dimensional images can be used.
[0035] In the disclosed examples, time-varying magnetic fields are
used to induce electric currents (eddy currents) in conductive
specimens of interest. A significant application is to produce eddy
currents in the brain or other organs, referred to herein as
electromagnetically induced Tumor Treating Field (TTF) therapy.
Image information and electromagnetic modeling can be used to
identify specimen/subject characteristics for a particular
specimen/subject and determine exposure characteristics such as
induced field strengths, coil currents, frequency, field
orientation(s).
[0036] The distribution of electromagnetically induced Tumor
Treating Field (TTF) therapy can be predicted and optimized using
various mathematical and computational modeling means, such as the
Finite Element Method (FEM). Such models can incorporate coil
geometry and properties, as well as head morphology and geometry,
and head electromagnetic properties to predict the distribution of
induced electric field and currents within the brain or other
tissue.
[0037] Referring to FIG. 1, a system for applying fields to a
specimen or patient includes an imaging system 102 that is arranged
so as to produce an image of a selected portion of a specimen. For
example, one or more brain areas of a patient can be imaged to
identify regions to which application of fields can be used for
treatment. The imaging system can be an X-ray system such as an
X-ray computed tomography (X-ray CT) system, a positron emission
tomography (PET) imaging system, an ultrasonic imager, a
single-photon emission computed tomography (SPECT) system, an MRI
system, or other imaging system that produces images suitable for
specimen evaluation. Typically, the imaging system stores a
specimen image in an image database in a memory 103 or other
storage device. A processor/controller 104 is coupled to the memory
103 so as to access one or more stored images. In some examples,
then processor 104 is configured to identify areas of the specimen
for treatment based on one or more image characteristics. However,
in other examples, the imaging system 102 is configured to provide
an indication of particular specimen areas for treatment. Such
areas can be noted as highlighted in a stored image (for example,
as colored or light/dark areas as displayed), or a table or other
listing of specimen areas can be stored as well. Identification can
be based on clinician evaluation or an automated image evaluation
process. In some cases, treatment locations are provided to the
processor/controller 104 as a series of image coordinates, or as
defined treatment volumes.
[0038] With areas for treatment identified by the
processor/controller 104, appropriate exposure fields are selected
based on characteristics stored in a treatment database 106. The
database 106 can store field magnitudes, durations pulse shapes,
repetition rates, pulse periods, pulse frequencies or frequency
spreads, field type, interpulse durations, or other pulse
characteristics. The treatment database can store such parameters
for a plurality of specimen conditions so that suitable values can
be selected for a particular specimen and specimen condition. For
example, a specimen database 108 can store specimen characteristics
such as specimen conductivity and magnetic permeability, density,
composition, orientation, or other features as a function of
location. Specimen characteristics can be used by the
processor/controller 104 in determining exposure fields to
compensate for field attenuation or enhancement due to local
specimen properties. Local variations in density, composition, or
specimen anisotropies can be used to modify applied field
characteristics so that intended fields tend to reach targeted
specimen locations. In some examples, the field generator 110 can
be controlled to vary a position of an intended field by
application of suitable electrical signals to one or more devices
such as coils. By selectively activating a plurality of field
coils, a specimen area can be exposed to an intended field without
requiring field coil or specimen movement. However, a scanning
system 112 can be provided to produce relative movement between
field coils and a specimen to facilitate treatment of extended
specimen regions.
[0039] In treatment of GBM, MRI or X-ray CT imaging systems can be
used to identify lesions that can be associated with GBM tissues.
More reliable identification of GBM lesions generally is based on
biopsy results. In some cases, perfusion or diffusion MRI and MR
spectroscopic measurements of metabolite concentrations can be used
as well. Surgical removal of GBM tissues can be used, with or
without tumor contrast enhancement using a fluorescent dye such as
5-aminolevulinic acid. These procedures also permit collection of
location data for subsequent use in defining electromagnetic field
exposures. Suitable stereotactic procedures can also be used to
locate areas for treatment.
[0040] A representative method 200 is illustrated in FIG. 2. At
210, a subject is assessed based on, for example, one or more
subject images or other subject evaluations. Based on the subject
assessment, at 220 one or more subject regions are identified for
treatment. The identified regions can be associated with diseased
tissues such as malignancies, or other regions for which treatment
is deemed appropriate. At 230, field characteristics such as pulse
duration or field magnitude are selected for application to the
identified regions. Different field characteristics can be
identified for some or all regions. Typically, preferred treatment
conditions can be provided based on parameters associated with
tissue characteristics, disease type, region location in the
subject and other characteristics that are stored in a database
232. At 240, the fields are applied.
[0041] Various configurations of magnetic fields can be applied.
Field frequencies of between 1 Hz and 100 MHz, 10 Hz and 10 MHz.
100 Hz and 1 MHz, 1 kHz and 1 MHz, 50 kHz and 1 MHz, 50 kHz and 500
kHz, 100 kHz and 500 kHz, and 100 kHz and 300 kHz are typically
used. Magnetic field amplitudes (and rates of change) are selected
to produce treatment electric field strengths of between 0.1 V/cm
and 100 V/cm, 0.5 V/cm and 20 V/cm, 1 V/cm and 10 V/cm, or 1 V/cm
and 3 V/cm. Magnetic fields selected to produce electric field
magnitudes of at least 0.5, 1, 2, or 5 V/cm are generally preferred
for effective disruption of mitotic division processes in GBM or
other cancers. Coupling of time-varying magnetic fields into the
brain (including deep brain areas) tends not to be limited by
conductive pathways that can shunt applied fields away from a
selected target region. Direct contact with the scalp, such as low
resistance electrical contact with conductive gels or other
materials, is not required. TTF generating coils can be placed
comfortably around the scalp without coil-to-skin contact required
or the patient's hair to be shaven. Induced electric fields can
more readily provide whole brain coverage, are more readily steered
in both direction and distribution.
[0042] A representative apparatus for applying fields is shown in
FIGS. 3A-3B. Coils 302-306 are situated about a target region 301
so that fields can be applied based on an energization of a
selected one or more of the coils 302-306. Typically, the coils
302-306 are secured to a hollow frame 310 so that the coils 320-306
can be maintained at a fixed spatial relationship with respect to
each other and with respect to the target region 301. The coils
302-306 may or may not contact a specimen situated in the target
region 301. A generator 312 selectively couples electrical signals
to the coils 302-306 via a switch 313 to produce field
distributions in the target region 301. As noted above, the fields
are generally configured based on determinations made in a
controller 314. In some examples, only a few coils are provided,
and are movable with respect to the hollow frame 310 for
positioning to target a particular specimen volume.
[0043] In the example configuration of FIG. 3A, the frame 310 is
spaced apart from the target region with spacers 320, 321. In
typical examples, the frame is a rigid shell such as a helmet, and
the spacers 320, 321 are made of compliant, thermally insulating
materials such as a foam so as to space the frame 310 and coils
302-306 away from a head of a patient. Two separate spacers are
shown in FIG. 3A, but more spacers can be used, or spacers such as
spacer pads or strips, or a continuous layer of spacer material can
be secured to the frame 310. If desired, a volume 330 between the
subject's head and the frame 310 can be filled with an insulating
material to provide comfort, especially in applications in which
the coils 302-306 may generate appreciable heat during operation.
Alternatively, the volume 330 can be left open and a fan or other
device can be situated to provide a cooling flow of air, and the
frame 310 can be provided with cut-outs that permit airflow through
the frame 310. In addition, one or more temperature sensors such as
temperature sensor 332 can be coupled to the controller 314 so that
excessive temperatures are not reached. In some examples, each of
the coils 302-306 is provided with a temperature sensor that is
coupled to the controller 314.
[0044] In an alternative arrangement shown in FIG. 4,
electromagnetic TTF generating coils 402-406 are secured to a
helmet 410. A controller 414 is coupled to the coils 402-406 so as
to apply selected sequences or series of waveforms to a specimen
situated in a target region 401. The electromagnetic TTF generating
system 402 includes a pulse generator 402A and a coil 402B that
produces a time varying magnetic field in response to electrical
pulses from the pulse generator 402A. With this apparatus, pulse
generators and coils can be secured the helmet. If desired, the
controller 414 can be secured to the helmet 410 as well. Pulse
generators and coils can be configured as described in Boyden et
al., U.S. Patent Application Publication 2009/0018384 or, Schneider
et al., U.S. Pat. No. 8,523,753, both of which are incorporated
herein by reference. In some embodiments, the electromagnetic TTF
generating system 402 includes a battery and thus the apparatus can
be used without wired power connections. The helmet 410 can include
straps, pads, or other features so as to secure the helmet 410 and
coils or the electromagnetic TTF generator 402-406 with respect to
the target region 401 so as to provide electromagnetic fields to a
selected portion of a subject's brain.
[0045] Data storage 420 can be provided as, for example, random
access or other memory that stores pulse characteristics (duration,
field strength, time of application, frequency of application) to
be used by the controller 414 in activating electromagnetic TTF
generating system. In addition, the data storage can be used to
record and confirm application of fields so that a clinician can
verify exposures. One or more user interface devices such as
switches, displays, touch screens, indicator lights, audible
alarms, vibration devices, or other devices that provide visible,
audible, or tactile indications of device activity. The storage 420
can be provided as removable storage as a USB memory or a memory
card.
[0046] In another example shown in FIG. 5, a transceiver 510 is
coupled to a controller 511, and both are secured to a helmet 508
that can be fixed to the head of a patient so as to permit
exposures to electromagnetic fields within a region 501 by
energizing coils 502-506. Treatment field prescriptions and/or
pulse sequences can be stored in a memory 512, which is also
secured to the helmet 508. An antenna 516 is coupled to the
transceiver 510 so as to send and receive signals from an antenna
519 that is coupled to a transceiver 520 of a mobile computing
device 521. As shown in FIG. 5, a treatment apparatus is secured to
a helmet to form a portable apparatus that can provide lengthy
treatments, but still provide patient comfort and mobility.
[0047] Other mounting configurations can be used to fix a treatment
apparatus with respect the head of the patient. Referring to FIG.
6, coils 602-608 are retained in a compliant spacer layer 610
situated about a target space 614. A protective layer 616 or a
rigid shell can be secured to the spacer layer 610, if desired. The
spacer layer 610 can have a predetermined shape so as to
substantially correspond to an average patient head. In still other
examples, the coils (and associated circuitry) can be secured to a
flexible support such as cloth that can serve as a head covering.
Hats of various configurations can be used as well. Such
arrangements make application of treatment fields over long
durations practical and convenient. For applications to other
areas, coils can be secured to or by any form filling garment such
as socks, bras, compression shirts, tights, leggings, gloves,
headbands, scarves, or other clothing items. In other examples,
coils can be provided in cushions or other objects that are not
secured to the subject, but which are convenient for exposure,
particularly long exposures.
[0048] FIG. 7 shows a screen shot 700 of an exemplary user
interface for obtaining treatment field generating currents or
voltages. A checkbox 702 is provided for selecting an appropriate
treatment frequency in a drop down menu 704. As shown, continuous
treatment is selected, but treatment repetition can be selected so
as to be periodic or aperiodic, and time of day for treatment can
also be selected. While default values for treatment fields can be
used, custom field strengths can be selected with checkbox 706, and
input into a data entry box 708. Spatial location of treatment
areas can be obtained from a patient image such as a magnetic
resonance image selected using checkbox 710; spatial coordinates
based on spatial coordinates or other data can be selected with
checkboxes 712, 715, respectively, and any associated data or image
files selected for input by clicking a button 714. Data entry can
be accepted or rejected with buttons 716, 718. The user interface
can also be used to receive externally generated treatment
conditions. Based on data input with the user interface, suitable
drive levels for treatment field generation are obtained for a
treatment device that is selectable with a drop down menu 720.
Using MRI and other imaging data, personalized computational
electrical models of the brain or other body organs or parts based
on an individual's imaging data can be used to specify doses and
estimate possible tissue responses to TTFs.
[0049] FIG. 8 and the following discussion are intended to provide
a brief, general description of an exemplary computing environment
in which the disclosed technology may be implemented. Typically,
FEM or other electromagnetic field modeling applications are used
to establish preferred currents or current sequences that target
selected areas for treatment. Although not required, the disclosed
technology is described in the general context of computer
executable instructions, such as program modules, being executed by
a personal computer (PC). Generally, program modules include
routines, programs, objects, components, data structures, etc.,
that perform particular tasks or implement particular abstract data
types. Moreover, the disclosed technology may be implemented with
other computer system configurations, including hand held devices,
multiprocessor systems, microprocessor-based or programmable
consumer electronics, network PCs, minicomputers, mainframe
computers, and the like. The disclosed technology may also be
practiced in distributed computing environments where tasks are
performed by remote processing devices that are linked through a
communications network. In a distributed computing environment,
program modules may be located in both local and remote memory
storage devices.
[0050] With reference to FIG. 8, an exemplary system for
implementing the disclosed technology includes a general purpose
computing device in the form of an exemplary conventional PC 800,
including one or more processing units 802, a system memory 804,
and a system bus 806 that couples various system components
including the system memory 804 to the one or more processing units
802. The system bus 806 may be any of several types of bus
structures including a memory bus or memory controller, a
peripheral bus, and a local bus using any of a variety of bus
architectures. The exemplary system memory 804 includes read only
memory (ROM) 808 and random access memory (RAM) 810. A basic
input/output system (BIOS) 812, containing the basic routines that
help with the transfer of information between elements within the
PC 800, is stored in ROM 808. The memory 804 also includes a memory
portion 811A that stores computer-executable instructions for
computing coil currents or other field stimuli so as to achieve
effective field strengths at target areas. The resulting field data
can be stored in the memory 804 at memory portion 811B. The field
data can also include prescribed exposure conditions for use by the
field calculator. In some examples, field calculations are based on
individual subject images or image data stored in memory 811C or
obtained over a local area or wide area network. Such field
calculations can include tissue inhomogeneity, tissue boundaries,
tissue orientations, and other features that are common to all
subjects or specific to an individual subject. One example of such
computations is described in Miranda et al., "Tissue heterogeneity
as a mechanism for localized neural stimulation by applied electric
fields," Phys. Med. Biol. 52:5603-5617 (2007). These individualized
field calculations can be performed at various network locations,
or by the device used to apply TTFs.
[0051] The magnitude, direction and distribution of induced
electric fields in a tissue can be important determinants of
treatment efficacy. These field characteristics can be estimated
based on image data or other patient-specific data. For example,
for treatment of brain cancer, a numerical head model can be
created from one or more MRIs. Voxel size can be selected as
needed, and in one example, a voxel size of 1 mm.sup.3 is selected.
MRIs can be segmented into different tissue types such as scalp,
skull, cerebrospinal fluid (CSF), gray matter (GM), and white
matter (WM). In some cases, data for head models can be obtained
with electrode arrays or pairs of such arrays placed on the scalp,
and currents can be applied to the electrodes with a selected
frequency and amplitude, such as at about 200 kHz and 100 mA. The
magnitude of the electric field is typically higher in white matter
because its impedance is higher than that of gray matter. The low
impedance of CSF in the ventricles also affects the electric field
in nearby brain tissue. The electric field is not uniform as it is
affected by the distribution of tissue types, the location and
orientation of interfaces between them, and their individual
electrical properties. As a result of tissue heterogeneity,
shunting as well as concentration of current and electric field can
be observed in different parts of the brain. The inclusion of
anisotropy in the electrical conductivity of white matter in models
can be used to further quantify shunting and spatial
non-uniformity.
[0052] In some examples, induced fields having time-varying
directions and at two or more frequencies can be used. For example,
a field direction can vary during a single field application or
vary from exposure to exposure. Each field direction can be
associated with a different field magnitude, if desired. Similarly,
a single field application can have a plurality of frequency
components, or a series of different frequencies can be
applied.
[0053] The exemplary PC 800 further includes one or more storage
devices 830 such as a hard disk drive for reading from and writing
to a hard disk, a magnetic disk drive for reading from or writing
to a removable magnetic disk, and an optical disk drive for reading
from or writing to a removable optical disk (such as a CD-ROM or
other optical media). Such storage devices can be connected to the
system bus 806 by a hard disk drive interface, a magnetic disk
drive interface, and an optical drive interface, respectively. The
drives and their associated computer readable media provide
nonvolatile storage of computer-readable instructions, data
structures, program modules, and other data for the PC 800. Other
types of computer-readable media which can store data that is
accessible by a PC, such as magnetic cassettes, flash memory cards,
digital video disks, CDs, DVDs, RAMs, ROMs, and the like, may also
be used in the exemplary operating environment.
[0054] A number of program modules may be stored in the storage
devices 830 including an operating system, one or more application
programs, other program modules, and program data. In some
examples, electromagnetic field calculation applications such as
finite element method calculators are stored in the storage device
830. A user may enter commands and information into the PC 800
through one or more input devices 840 such as a keyboard and a
pointing device such as a mouse. Other input devices may include a
digital camera, microphone, joystick, game pad, satellite dish,
scanner, or the like. These and other input devices are often
connected to the one or more processing units 802 through a serial
port interface that is coupled to the system bus 806, but may be
connected by other interfaces such as a parallel port, game port,
or universal serial bus (USB). A monitor 846 or other type of
display device is also connected to the system bus 806 via an
interface, such as a video adapter. Other peripheral output
devices, such as speakers and printers (not shown), may be
included.
[0055] The PC 800 may operate in a networked environment using
logical connections to one or more remote computers, such as a
remote computer 860. In some examples, one or more network or
communication connections 850 are included. The remote computer 860
may be another PC, a server, a router, a network PC, or a peer
device or other common network node, and typically includes many or
all of the elements described above relative to the PC 800,
although only a memory storage device 862 has been illustrated in
FIG. 8. The personal computer 800 and/or the remote computer 860
can be connected to a logical a local area network (LAN) and a wide
area network (WAN). Such networking environments are commonplace in
offices, enterprise wide computer networks, intranets, and the
Internet. A field generator 860 (such as coils and associated drive
circuitry) can be coupled to the PC 800, but in many cases, the
field generator 860 is activated according to instructions produced
using the field calculator, but is not connected to the PC 800.
[0056] When used in a LAN networking environment, the PC 800 is
connected to the LAN through a network interface. When used in a
WAN networking environment, the PC 800 typically includes a modem
or other means for establishing communications over the WAN, such
as the Internet. In a networked environment, program modules
depicted relative to the personal computer 800, or portions
thereof, may be stored in the remote memory storage device or other
locations on the LAN or WAN. The network connections shown are
exemplary, and other means of establishing a communications link
between the computers may be used.
[0057] FIG.9 is a system diagram depicting an exemplary mobile
device 900 including a variety of optional hardware and software
components, shown generally at 902. Any components 902 in the
mobile device can communicate with any other component, although
not all connections are shown, for ease of illustration. The mobile
device can be any of a variety of computing devices (e.g., cell
phone, smartphone, handheld computer, Personal Digital Assistant
(PDA), etc.) and can allow wireless two-way communications with one
or more mobile communications networks 904, such as a cellular or
satellite network.
[0058] The illustrated mobile device 900 can include a controller
or processor 910 (e.g., signal processor, microprocessor, ASIC, or
other control and processing logic circuitry) for performing such
tasks as signal coding, data processing, input/output processing,
power control, and/or other functions. An operating system 912 can
control the allocation and usage of the components 902 and support
for one or more application programs 914. As shown in FIG. 9, the
application programs include applications that receive treatment
data from a clinician, compute drive levels required for treatment,
perform FEM or other modeling of volumes to be treated, and record
treatment history. The application programs can also include common
mobile computing applications (e.g., email applications, calendars,
contact managers, web browsers, messaging applications), or any
other computing application to be used in conjunction with
treatment applications to send and receive treatment prescriptions,
field calculations, drive levels, and confirmations of treatment
status.
[0059] The illustrated mobile device 900 can include memory 920.
Memory 920 can include non-removable memory 922 and/or removable
memory 924. The non-removable memory 922 can include RAM, ROM,
flash memory, a hard disk, or other well-known memory storage
technologies. The removable memory 924 can include flash memory or
a Subscriber Identity Module (SIM) card, which is well known in GSM
communication systems, or other well-known memory storage
technologies, such as "smart cards." The memory 920 can be used for
storing data and/or code for running the operating system 912 and
the applications 914. Example data can include web pages, text,
images, sound files, video data, or other data sets to be sent to
and/or received from one or more network servers or other devices
via one or more wired or wireless networks. The memory 920 can be
used to store a subscriber identifier, such as an International
Mobile Subscriber Identity (IMSI), and an equipment identifier,
such as an International Mobile Equipment Identifier (IMEI). Such
identifiers can be transmitted to a network server to identify
users and equipment. Treatment prescriptions can be stored in the
memory 920.
[0060] The mobile device 900 can support one or more input devices
930, such as a touchscreen 932, microphone 934, camera 936,
physical keyboard 938 and/or trackball 940 and one or more output
devices 950, such as a speaker 952 and a display 954. Other
possible output devices (not shown) can include piezoelectric or
other haptic output devices. Some devices can serve more than one
input/output function. For example, touchscreen 932 and display 954
can be combined in a single input/output device. The input devices
930 can include a Natural User Interface (NUI). An NUI is any
interface technology that enables a user to interact with a device
in a "natural" manner, free from artificial constraints imposed by
input devices such as mice, keyboards, remote controls, and the
like. Examples of NUI methods include those relying on speech
recognition, touch and stylus recognition, gesture recognition both
on screen and adjacent to the screen, air gestures, head and eye
tracking, voice and speech, vision, touch, gestures, and machine
intelligence. Other examples of a NUI include motion gesture
detection using accelerometers/gyroscopes, facial recognition, 3D
displays, head, eye, and gaze tracking, immersive augmented reality
and virtual reality systems, all of which provide a more natural
interface, as well as technologies for sensing brain activity using
electric field sensing electrodes (EEG and related methods). Thus,
in one specific example, the operating system 912 or applications
914 can comprise speech-recognition software as part of a voice
user interface that allows a user to operate the device 900 via
voice commands. Further, the device 900 can comprise input devices
and software that allows for user interaction via a user's spatial
gestures.
[0061] A wireless modem 960 can be coupled to an antenna (not
shown) and can support two-way communications between the processor
910 and external devices, as is well understood in the art. The
modem 960 is shown generically and can include a cellular modem for
communicating with the mobile communication network 904 and/or
other radio-based modems (e.g., Bluetooth 964 or Wi-Fi 962). The
wireless modem 960 is typically configured for communication with
one or more cellular networks, such as a GSM network for data and
voice communications within a single cellular network, between
cellular networks, or between the mobile device and a public
switched telephone network (PSTN).
[0062] The mobile device can further include at least one
input/output port 980, a power supply 982, a satellite navigation
system receiver 984, such as a Global Positioning System (GPS)
receiver, an accelerometer 986, and/or a physical connector 990,
which can be a USB port, IEEE 1394 (FireWire) port, and/or RS-232
port. The illustrated components 902 are not required or
all-inclusive, as any components can be deleted and other
components can be added.
[0063] FIG. 10 illustrates a generalized example of a suitable
implementation environment 1000 in which described embodiments,
techniques, and technologies may be implemented. In example
environment 1000, various types of services (e.g., computing
services) are provided by a cloud 1010. For example, the cloud 1010
can comprise a collection of computing devices, which may be
located centrally or distributed, that provide cloud-based services
to various types of users and devices connected via a network such
as the Internet. These devices can be coupled to diagnostic devices
such as magnetic resonance imaging devices, finite element field
and current calculators, as well as treatment devices and clinician
record keeping systems. The implementation environment 1000 can be
used in different ways to accomplish computing tasks. For example,
some tasks (e.g., processing user input and presenting a user
interface) can be performed on local computing devices (e.g.,
connected devices 1030, 1040, 1050) while other tasks (e.g.,
storage of data to be used in subsequent processing) can be
performed in the cloud 1010. For example, connected device 1040 can
be used to provide instructions to a treatment device 1050.
[0064] In example environment 1000, the cloud 1010 provides
services for connected devices 1030, 1040, 1050 with a variety of
screen capabilities. Connected device 1030 represents a device with
a computer screen 1035 (e.g., a mid-size screen). For example,
connected device 1030 could be a personal computer such as desktop
computer, laptop, notebook, netbook, or the like. Connected device
1040 represents a device with a mobile device screen 1045 (e.g., a
small size screen). For example, connected device 1040 could be a
mobile phone, smart phone, personal digital assistant, tablet
computer, or the like. Connected device 1050 represents a device
with a large screen 1055. For example, connected device 1050 could
be a television screen (e.g., a smart television) or another device
connected to a television (e.g., a set-top box or the like. One or
more of the connected devices 1030, 1040, 1050 can include
touchscreen capabilities. Touchscreens can accept input in
different ways. For example, capacitive touchscreens detect touch
input when an object (e.g., a fingertip or stylus) distorts or
interrupts an electrical current running across the surface. As
another example, touchscreens can use optical sensors to detect
touch input when beams from the optical sensors are interrupted.
Physical contact with the surface of the screen is not necessary
for input to be detected by some touchscreens. Devices without
screen capabilities also can be used in example environment 1000.
For example, the cloud 1010 can provide services for one or more
computers (e.g., server computers) without displays.
[0065] Services can be provided by the cloud 1010 through service
providers such as a clinical services provider 1020, or through
other providers of online services (not depicted). For example,
cloud services can be customized to the screen size, display
capability, and/or touchscreen capability of a particular connected
device (e.g., connected devices 1030, 1040, 1050) for communication
with treating physicians.
[0066] In some cases, individualized electric field distributions
are determined for a particular treatment based on one or more
electrical characteristics of a region to be treated. Such
distributions can be based on specimen image such as magnetic
resonance imaging or computed tomography. Tissue properties in a
region to be treated can be characterized to estimate conductivity,
dielectric constants, and frequency response. Then, exposures can
be personalized as to duration, orientation, magnitude, and
frequency.
[0067] FIG. 11 illustrates a representative coil assembly 1100 that
includes a plurality of coils 1102-1107 that are electrically
coupled to a current source 1110. The coils 1102-1107 can be
rigidly or flexibly coupled with connectors 1112-1122 that can also
serve as electrical connectors or including switches or switching
circuit to permit selection of particular coils to be energized.
Additional coils and coils of difference sizes and shapes can be
used. As shown in FIG. 11, the coils 1102-1107 include current
paths having different diameters so that areas associated with
magnetic field variations can be selected. The coils 1102-1107 can
have selectable diameters or can include one or more subcoils.
Coils can define rectangular, polygonal, oval, elliptical,
circular, or other current paths that comprise one or more straight
line or curved segments. The coils assembly 1100 can include coils
arranged for exposure of a selected region to time-varying magnetic
fields to produce induced electric fields. Different regions of a
subject can be exposed (e.g., arms, head, torso, ankles, wrists,
legs) or coils can be arranged for exposure of various organs or
tissues (e.g., brain, stomach, lungs). In one example, coils can be
associated with selected hexagons and pentagons of a truncated
icosahedron to enclose or partially enclose a specimen volume. A
soccer ball coil configuration for use in magnetic resonance
imaging is described in Wiggins et al., "32-channel 3 Tesla
receive-only phased-array head coil with soccer-ball element
geometry," Magn. Res. Med. 56:216-23 (2006). In still other
examples, smaller numbers of coils can be used, and situated to
produce induced electric fields so as to target particular regions.
Current waveforms and amplitudes could be controlled individually
for each coil.
[0068] Application of induced fields may be more effective if the
induced fields are suitably aligned. Absent a known, predetermined
alignment of a specimen or subject region to be exposed, applied
field directions can be varied as illustrated schematically in FIG.
12. Coils 1202, 1204 are situated to produce magnetic fields in a
specimen volume 1201 along a first axis 1205, such as an
anterior-posterior axis. Coils 1206, 1208 are situated to produce
magnetic fields in the specimen volume 1201 along a second axis
1209, such as a left-right axis. Additional coils and axes can be
used, and varying directions can be achieved with multiple coils or
coil sets, or by adjusting a relative orientation of the specimen
volume 1201 with respect to one or more coils.
[0069] One or more coils can be energized at a single frequency or
a swept frequency to produce induced fields at a single frequency
or multiple frequencies. Coils can be arranged to induce electric
fields in two or more directions simultaneously although care must
generally be taken so that multiple induced fields do not tend to
cancel.
[0070] A representative TTF exposure method 1300 includes storing a
set of specimen characteristics at 1302. Such as electrical and
structural characteristics can be obtained by specimen imaging or
other processes. A specimen model is obtained at 1304 and suitable
exposure characteristics are selected at 1306. Various
characteristics can be selected from a set of exposure values
stored at 1308. Corresponding currents are selected at 1310 and
delivered to coils sets such as left/right coils 1312 and
anterior/posterior coils 1314.
[0071] In view of the many possible embodiments to which the
principles of the disclosed technology may be applied, it should be
recognized that the illustrated embodiments are only preferred
examples and should not be taken as limiting the scope of the
invention. We therefore claim as our invention all that comes
within the scope and spirit of these claims.
* * * * *